Dr. Croce entered the school of medicine of La Sapienza University of Rome and graduated in 1969 summa cum laude  in medicine and Latin. He began his career in the United States the following year as an associate scientist at the Wistar Institute of Biology and Anatomy in Philadelphia. In 1980, he was named Wistar Professor of Genetics at the University of Pennsylvania and associate director of the Wistar Institute, titles he held until 1988. He was at Wistar from 18 years. From 1988-91, he was director of the Fels Institute for Cancer Research and Molecular Biology at Temple University School of Medicine in Philadelphia. Croce rapidly expanded the faculty and staff and launched a PhD programme in genetics.

In 1991, Croce was named Director of the Kimmel Cancer Center at Jefferson Medical College at the Thomas Jefferson University in Philadelphia. While at Jefferson, he discovered in 2002 the role of microRNAs in cancer pathogenesis and progression, implicating a new class of genes in cancer causation – he found that loss of two miRNAs that target BCL2 caused chronic lymphocytic leukemia in mice.

In 2004, Croce moved to Ohio State University, where he had been an external advisor since 1988. Under his direction, the faculty within the Human Cancer Genetics Program conduct both clinical and basic research. Basic research projects focus on how genes are activated and inactivated, how cell-growth signals are transmitted and regulated within cells, and how cells interact with the immune system. Clinical research focuses on discovering genes linked to cancer and mutations that predispose people to cancer.

Dr. Corce is noted for research into the genetic mechanisms of cancer. His work focuses on microRNAs and their role in oncology. He discovered the juxtaposition of the human immunoglobulin genes to the MYC oncogene and the deregulation of MYC in Burkitt lymphoma; the MLL gene involved in acute leukemias; the TCL1A gene associated with T-cell leukemias; and cloned, named and characterized the BCL2 gene involved in follicular lymphoma. Croce also uncovered early events involved in the pathogenesis of lung, nasopharyngeal, head and neck, esophageal, gastrointestinal and breast cancers.

Dr. Croce received numerous awards, including the 2006 Clowes Memorial Award from the American Association for Cancer Research for his discoveries of the molecular mechanisms of leukemia. In 2010, he was elected a fellow of the American Academy of Arts and Sciences. He received the Szent-Györgyi Prize for Progress in Cancer Research (2011), the Outstanding Investigator Award from National Cancer Institute (2015) and the Dan David Award (2018).